Cell function and gene expression are controlled through complex and dynamic interactions between cells and their surrounding extracellular matrix. Hence, the successful construction of engineered cell or tissue analogs requires the re-creation of a biologically active extracellular environment in which to develop the product. Ultrasound therapy is currently used clinically to promote bone healing and has been shown to enhance soft tissue repair. Some biological effects of ultrasound are known to result from the mechanical forces associated with acoustic wave propagation. In vitro studies demonstrate that mechanical stresses positively affect both extracellular matrix organization and cell behavior. Thus, we hypothesize that acoustically-driven mechanical forces can be used to control extracellular matrix deposition and promote cell and tissue function. In this joint, exploratory proposal, we will combine our knowledge of extracellular matrix biology and biomedical ultrasound to determine the acoustic and biochemical mechanisms by which ultrasound affects extracellular matrix remodeling and cell function. In Aim 1, we will characterize and optimize the acoustic parameters that influence extracellular matrix remodeling. In conjunction with this aim, parallel studies in Aim 2 will focus on biochemically characterizing the effects of ultrasound on the deposition and structural organization of fibronectin and collagen I fibrils in the extracellular matrix. In Aim 3, we will use optimized acoustic fields to stimulate extracellular matrix organization in order to engineer the biological and material properties of a collagen-based tissue construct.